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Evaluating the Safety and Pharmacokinetics of VRC01 and VRC01LS, Potent Anti-HIV Neutralizing Monoclonal Antibodies, in HIV-1-Exposed Infants

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ClinicalTrials.gov Identifier: NCT02256631
Recruitment Status : Recruiting
First Posted : October 3, 2014
Last Update Posted : August 3, 2018
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Brief Summary:
The purpose of this study is to assess the safety and pharmacokinetics (PK) of two monoclonal antibodies, VRC01 and VRC01LS, in HIV-exposed infants who are at increased risk of mother-to-child HIV transmission.

Condition or disease Intervention/treatment Phase
HIV Infections Biological: VRC01 Biological: VRC01LS Phase 1

Detailed Description:

VRC01 and VRC01LS are anti-HIV neutralizing monoclonal antibodies that may help prevent mother-to-child transmission of HIV. This study will enroll HIV-infected mothers who are at increased risk of passing HIV on to their children. The purpose of this study is to assess the safety and PK of VRC01 and VRC01LS in HIV-exposed infants.

This study will enroll mother-infant pairs into four groups. Infants enrolled in Dose Group 1 and Dose Group 2 will receive a single VRC01 injection less than 72 hours after birth. Infants in Dose Group 3 will receive a VRC01 injection less than 5 days after birth. They will then receive additional VRC01 injections monthly for at least 6 months and no more than 18 months while breastfeeding. Infants will enroll into one of two cohorts in Dose Group 4: Cohort 1 (non-breastfeeding) or Cohort 2 (breastfeeding). Infants in Cohort 1 will receive a single VRC01LS injection less than 72 hours after birth. Infants in Cohort 2 will receive an initial VRC01LS injection less than 5 days after birth, and a second VRC01LS injection at Week 12 if they are still breastfeeding.

The mothers will not receive any VRC01 or VRC01LS injections. At study entry, all mothers will undergo a medical history review and a blood collection. Infants in Dose Groups 1 and 2 will attend several study visits through Week 48. Infants in Dose Group 3 and 4 will attend several study visits through Week 96. Visits will include a medical history review, physical examination, blood collection, and oral fluid collection.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 118 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Open-Label, Dose-Escalating, Phase I Study to Determine Safety and Pharmacokinetic Parameters of Subcutaneous (SC) VRC01 and VRC01LS, Potent Anti-HIV Neutralizing Monoclonal Antibodies, in HIV-1-Exposed Infants
Study Start Date : April 2015
Estimated Primary Completion Date : April 30, 2020
Estimated Study Completion Date : December 30, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
Experimental: Dose Group 1
Infants in Dose Group 1 will receive a single VRC01 20 mg/kg injection less than 72 hours after birth.
Biological: VRC01
Administered by subcutaneous injection in the thigh
Other Names:
  • VRC-HIVMAB-060-00-AB
  • VRC01 mAb

Experimental: Dose Group 2
Infants in Dose Group 2 will receive a single VRC01 40 mg/kg injection less than 72 hours after birth.
Biological: VRC01
Administered by subcutaneous injection in the thigh
Other Names:
  • VRC-HIVMAB-060-00-AB
  • VRC01 mAb

Experimental: Dose Group 3
Infants in Dose Group 3 will receive a VRC01 40 mg/kg injection less than 5 days after birth. They will then receive a VRC01 20 mg/kg injection monthly for at least 6 months and no more than 18 months while breastfeeding.
Biological: VRC01
Administered by subcutaneous injection in the thigh
Other Names:
  • VRC-HIVMAB-060-00-AB
  • VRC01 mAb

Experimental: Dose Group 4
Infants in Cohort 1 will receive a single VRC01LS injection less than 72 hours after birth. Dose is based on weight: 80 mg for infants weighing less than 4.5 kg and 100 mg for infants weighing 4.5 kg or greater. Infants in Cohort 2 will receive an initial VRC01LS injection less than 5 days after birth, with dose based on weight. A second dose of 100 mg VRC01LS will be administered at Week 12 if an infant is still breastfeeding.
Biological: VRC01LS
Administered by subcutaneous injection in the thigh
Other Names:
  • VRC-HIVMAB080-00-AB
  • VRC01LS mAb




Primary Outcome Measures :
  1. Death (number of participants) [ Time Frame: Measured through participants' last study visit (at Week 48-96) ]
  2. Frequency of Grade 3 or higher adverse events [ Time Frame: Measured through participants' last study visit (at Week 48-96) ]
  3. Frequency of VRC01- or VRC01LS-related Grade 3 or higher adverse events [ Time Frame: Measured through participants' last study visit (at Week 48-96) ]
  4. Frequency of HIV infection diagnoses [ Time Frame: Measured through participants' last study visit (at Week 48-96) ]

Secondary Outcome Measures :
  1. Development of anti-VRC01 antibodies (yes/no) [ Time Frame: Measured through participants' last study visit (at Week 48-96) ]
  2. VRC01 antibody levels in oral secretions [ Time Frame: Measured through participants' last study visit (at Week 48-96) ]
  3. Development of anti-VRC01LS antibodies (yes/no) [ Time Frame: Measured through participants' last study visit (at Week 48-96) ]
  4. VRC01LS antibody levels in oral secretions [ Time Frame: Measured through participants' last study visit (at Week 48-96) ]


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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Maternal Inclusion Criteria:

  • Documentation of HIV infection. Documentation of HIV-1 infection is defined as positive results from two samples collected at different time points. All samples tested must be whole blood, serum, or plasma. For this protocol, the results for sample #2 may be pending at the time of enrollment. Results documented in the clinical record from past testing may be used to satisfy the criteria for documentation of HIV-1 infection. More information on this criterion can be found in the protocol.
  • Greater than or equal to 18 years of age
  • Able and willing to provide signed informed consent for herself and her infant

Maternal Exclusion Criteria:

  • Prior participation in any HIV-1 vaccine trial
  • Receipt of any other active or passive HIV immunotherapy or investigational product during this pregnancy. (Note that administration of Food and Drug Administration [FDA]-approved antiretroviral [ARV] drugs when used to treat disease or prevent mother-to-child transmission are not considered investigational.)
  • Documented or suspected serious medical illness or immediate life threatening condition (other than HIV infection) in the mother that may interfere with the ability to complete study requirements, as judged by the examining clinician

Infant Inclusion Criteria:

  • Born to an HIV-1-infected woman who meets all maternal inclusion/exclusion criteria listed above
  • Gestational age, by best obstetrical, ultrasound, or infant exam, greater than or equal to 36 weeks
  • Birth weight greater than or equal to 2.0 kg
  • Allowable infant age at the time of enrollment is dependent on the Dose Group and Cohort:

    • Dose Group 4 (Cohort 1): Less than 72 hours of age, and anticipated availability to receive VRC01 immunization at less than 72 hours after birth.
    • Dose Group 4 (Cohort 2): Less than or equal to 5 days of age, and anticipated availability to receive VRC01 immunization no more than 5 days after birth.
  • At increased risk of HIV acquisition defined as documentation of one or more of the following risk factors:
  • Dose Group 4 (Cohort 1), only:

    • Mother received no ART during pregnancy or mother began or reinitiated ART (after an interruption of greater than 14 days), during the third trimester of pregnancy; or
    • Mother with any detectable viral replication (HIV RNA above the limit of detection) at last measurement prior to delivery determined within 30 days of delivery; or
    • Prolonged rupture of membranes (greater than 12 hours); or
    • Mother with documented* 2-class resistant HIV infection, which may include historical documentation of lack of response
    • Women who have a documented history of virologic failure while on NNRTIs but who had no resistance testing at the time of viral failure will be considered to have NNRTI documented resistance.
  • Dose Group 4 (Cohort 2), only (African sites):

    • Mother intends to breastfeed

Infant Exclusion Criteria:

  • Receipt of any other active or passive HIV immunotherapy or investigational product other than the study vaccine (Note: Infant prophylaxis with any licensed ARV drugs clinically prescribed to prevent mother-to-child HIV transmission are not considered investigational.)
  • Receipt of or anticipated need for blood products, immunoglobulin, or immunosuppressive therapy. This includes infants who require hepatitis B immunoglobulin (HBIG) but does not require exclusion of infants who receive hepatitis B vaccine in the newborn period.
  • Documented or suspected serious medical illness, serious congenital anomaly, or immediate life threatening condition in the infant that may interfere with the ability to complete study requirements, as judged by the examining clinician
  • Any requirement for supplemental oxygen beyond 24 hours of life or requiring supplemental oxygen at the time of the VRC01 dose
  • Baseline laboratory results:

    • Hemoglobin less than 12.0 g/dL
    • Platelet count less than 100,000 cells/mm^3
    • Absolute neutrophil count: for infants less than or equal to 24 hours old, less than 4,000 cells/mm^3; for infants greater than 24 hours old, less than 1,250 cells/mm^3
    • Serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase [ALT]) greater than or equal to 1.25 times upper limit of age adjusted normal
  • Dose Group 4 (Cohort 1), only: Infant is breastfeeding at time of enrollment or mother has indicated an intention to initiate breastfeeding. Note: if a child is breastfed prior to known maternal diagnosis (in the case of a woman diagnosed in the intrapartum period), the child is still eligible as long as breastfeeding is stopped by the time the child is enrolled and there is no plan to resume breast milk feeding.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02256631


Locations
United States, California
University of California, UC San Diego CRS- Mother-Child-Adolescent HIV Program Not yet recruiting
La Jolla, California, United States, 92093-0672
Contact: Megan Loughran, B.A.    858-534-9218    meloughran@ucsd.edu   
Usc La Nichd Crs Not yet recruiting
Los Angeles, California, United States, 90089
Contact: Eva A. Operskalski, Ph.D.    323-865-1554    eva@usc.edu   
David Geffen School of Medicine at UCLA NICHD CRS Recruiting
Los Angeles, California, United States, 90095-1752
Contact: Michele F. Carter, B.S., R.N.    310-206-6369    mfcarter@mednet.ucla.edu   
United States, Colorado
Univ. of Colorado Denver NICHD CRS Recruiting
Aurora, Colorado, United States, 80045
Contact: Emily Barr, C.P.N.P., C.N.M., M.S.N.    720-777-6752    emily.barr@childrenscolorado.org   
United States, Florida
South Florida CDTC Ft Lauderdale NICHD CRS Recruiting
Fort Lauderdale, Florida, United States, 33316
Contact: Dayana Leon, L.P.N.    954-728-1054    dleon@browardhealth.org   
Univ. of Florida Jacksonville NICHD CRS Recruiting
Jacksonville, Florida, United States, 32209
Contact: Saniyyah Mahmoudi, A.R.N.P.    904-244-5331    saniyyah.mahmoudi@jax.ufl.edu   
Pediatric Perinatal HIV Clinical Trials Unit CRS Not yet recruiting
Miami, Florida, United States, 33136
Contact: Grace Alvarez    305-243-4447    galvarez2@miami.edu   
United States, Georgia
Emory University School of Medicine NICHD CRS Recruiting
Atlanta, Georgia, United States, 30322
Contact: LaTeshia Thomas-Seaton    404-616-5936    lseaton@emory.edu   
United States, Illinois
Lurie Children's Hospital of Chicago (LCH) CRS Not yet recruiting
Chicago, Illinois, United States, 60614-3393
Contact: Margaret Ann Sanders, M.P.H.    312-227-8275    msanders@luriechildrens.org   
United States, Maryland
Johns Hopkins Univ. Baltimore NICHD CRS Recruiting
Baltimore, Maryland, United States, 21287
Contact: Aleisha Collinson-Streng, R.N., A.C.R.N.    443-801-7301    acolli14@jhmi.edu   
United States, Massachusetts
Boston Medical Center Ped. HIV Program NICHD CRS Not yet recruiting
Boston, Massachusetts, United States, 02118
Contact: Debra McLaud, R.N.    617-414-5813    demclaud@bmc.org   
United States, New York
Bronx-Lebanon Hospital Center NICHD CRS Recruiting
Bronx, New York, United States, 10457
Contact: Martha Cavallo, A.N.P., C.R.N.P.    718-960-1010    mcavallo@bronxleb.org   
Jacobi Med. Ctr. Bronx NICHD CRS Recruiting
Bronx, New York, United States, 10461
Contact: Marlene Burey    718-918-4783    marlene.burey@nbhn.net   
United States, North Carolina
DUMC Ped. CRS Withdrawn
Durham, North Carolina, United States, 27710
United States, Pennsylvania
Philadelphia IMPAACT Unit CRS Withdrawn
Philadelphia, Pennsylvania, United States, 19104
United States, Texas
Texas Children's Hospital CRS Recruiting
Houston, Texas, United States, 77030-2399
Contact: Chivon D. McMullen-Jackson, B.S.N., A.D.N., R.N.    832-824-1339    cdmcmull@texaschildrens.org   
Puerto Rico
University of Puerto Rico Pediatric HIV/AIDS Research Program CRS Recruiting
San Juan, Puerto Rico, 00935
Contact: Ruth Santos, B.S.N., R.N., M.P.H.    1-787-759-9595    ruth.santos@upr.edu   
San Juan City Hosp. PR NICHD CRS Recruiting
San Juan, Puerto Rico, 00936
Contact: Lizbeth Fabregas-Troche, B.S., M.S.    787-764-3083    lfabregas@sanjuanciudadpatria.com   
South Africa
Fam-Cru Crs Recruiting
Tygerberg, Western Cape Province, South Africa, 7505
Contact: Joan Coetzee    27-21-9384157    joan@sun.ac.za   
Zimbabwe
Harare Family Care CRS Recruiting
Harare, Zimbabwe
Contact: Sukunena J. Maturure, RGN    263-712437682    sjmaturure@uzcrc.co.zw   
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
Investigators
Study Chair: Coleen Cunningham, MD Duke University

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT02256631     History of Changes
Other Study ID Numbers: IMPAACT P1112
11903 ( Registry Identifier: DAIDS ES )
First Posted: October 3, 2014    Key Record Dates
Last Update Posted: August 3, 2018
Last Verified: August 2018

Additional relevant MeSH terms:
HIV Infections
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Antibodies
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs